title: The inhibitory effects of bupivacaine, levobupivacaine, and ropivacaine on K2P (two-pore domain potassium) channel TREK-1.
abstract: OBJECTIVE
  Bupivacaine, levobupivacaine, and ropivacaine are amide local anesthetics. Levobupivacaine and ropivacaine are stereoisomers of bupivacaine and were developed to circumvent the bupivacaine's severe toxicity. The recently characterized background potassium channel, K(2P) TREK-1, is a well-known target for various local anesthetics. The purpose of study is to investigate the differences in inhibitory potency and stereoselectivity among bupivacaine, levobupivacaine, and ropivacaine on K(2P) TREK-1 channels overexpressed in COS-7 cells.
  
  
  METHODS
  We investigated the effects of bupivacaine, levobupivacaine, and ropivacaine (10, 50, 100, 200, and 400 μM) on TREK-1 channels expressed in COS-7 cells by using the whole cell patch clamp technique with a voltage ramp protocol ranging from -100 to 100 mV for 200 ms from a holding potential of -70 mV.
  
  
  RESULTS
  Bupivacaine, levobupivacaine, and ropivacaine showed reversible inhibition of TREK-1 channels in a concentration-dependent manner. The half-maximal inhibitory concentrations (IC(50)) of bupivacaine, levobupivacaine, and ropivacaine were 95.4 ± 14.6, 126.1 ± 24.5, and 402.7 ± 31.8 μM, respectively. IC(50) values indicated a rank order of potency (bupivacaine > levobupivacaine > ropivacaine) with stereoselectivity. Hill coefficients were 0.84, 0.93, and 0.89 for bupivacaine, levobupivacaine, and ropivacaine, respectively.
  
  
  CONCLUSIONS
  Inhibitory effects on TREK-1 channels by bupivacaine, levobupivacaine, and ropivacaine demonstrated stereoselectivity: bupivacaine was more potent than levobupivacaine and ropivacaine. Inhibition of TREK-1 channels and consecutive depolarization of the cell membrane by bupivacaine, levobupivacaine, and ropivacaine may contribute to the blockade of neuronal conduction and side effects.
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Shin
authors.forename: Jeong Seop
authors.initials: JS
authors.lastname: Soh
authors.forename: Hee Zoo
authors.initials: HZ
authors.lastname: Kim
authors.forename: Jinpyo
authors.initials: J
authors.lastname: Hong
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Woo
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Heo
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Lee
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D019556:COS Cells; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D000077554:Levobupivacaine; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors*; D000077212:Ropivacaine; D013237:Stereoisomerism
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D000077212:Ropivacaine; D000077554:Levobupivacaine; D002045:Bupivacaine